TRPC6 ameliorates renal ischemic reperfusion injury by targeting miR-214 to prevent caspase-1 expression

doi:10.3877/cma.j.issn.1674-0785.2022.01.015

Abstract

Abstract:

Objective

To investigate the alleviating effect and potential mechanism of TRPC6 on renal ischemic reperfusion injury (RIRI).

Methods

After establishing oxygen-glucose deprivation/reoxygenation, OGD/R HK-2 model cells and ischemia-reperfusion (I/R) model mice, the expression levels of IL-1β and IL-18 in model cells or mice were detected by using ELISA kits, whilst the expression of caspase-1 was examined by RT-qPCR, Western blot, and immunohistochemistry. And the cell viability and pyroptosis were determined by CCK-8 assay and flow cytometry. Moreover, the interaction between TRPC6 and miR-214 was identified by dual-luciferase reporter assay.

Results

The expression of TRPC6 was observably increased in OGD/R HK-2 cells and I/R model mice. Meanwhile, down-regulation of caspase-1 enhanced the vitality of OGD/R HK-2 cells and inhibited inflammation and pyroptosis. Overexpression of TRPC6 could alleviate renal injury and down-regulate caspase-1 in I/R model mice. TRPC6 could down-regulate caspase-1 partly by regulating miR-214, thereby improving RIRI.

Conclusion

TRPC6 alleviates RIRI by targeting miR-214 to down-regulate caspase-1 expression. The TRPC6/miR-214/caspase-1 regulatory pathway may provide key clues for the therapy of RIRI.

Key words: Renal ischemic reperfusion injury, TRPC6, MicroRNA-214, caspase-1, Pyroptosis

Youmin Pu, Hongwen Zhao, Bingbing Shen, Qiang Zhou, Pan Xie, Xiongfei Wu. TRPC6 ameliorates renal ischemic reperfusion injury by targeting miR-214 to prevent caspase-1 expression[J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(01): 84-93.

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URL: https://zhlcyszz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0785.2022.01.015

https://zhlcyszz.cma-cmc.com.cn/EN/Y2022/V16/I01/84

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